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This National Lipid Association (NLA) Expert Clinical Consensus provides an overview of the physiologic and clinical considerations regarding the role of apolipoprotein B (apoB) measurement to guide clinical care based on the available scientific evidence and expert opinion. ApoB represents the total concentration of atherogenic lipoprotein particles in the circulation and more accurately reflects the atherogenic burden of lipoproteins when compared to low-density lipoprotein cholesterol (LDL-C). ApoB is a validated clinical measurement that augments the information found in a standard lipoprotein lipid panel; therefore, there is clinical value in using apoB in conjunction with a standard lipoprotein lipid profile when assessing risk and managing lipid-lowering therapy (LLT). ApoB has been shown to be superior to LDL-C in risk assessment both before and during treatment with LLT. In individuals, there can be discordance between levels of LDL-C and apoB, as well as LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C), despite high levels of population-wide correlation. When there is discordance between LDL-C and apoB, or LDL-C and non-HDL-C, atherosclerotic cardiovascular disease risk generally aligns better with apoB or non-HDL-C. Additionally, apoB can be used in tandem with standard lipoprotein lipid measurements to diagnose distinct lipoprotein phenotypes. ApoB testing can inform clinical prognosis and care, as well as enable family cascade screening, when an inherited lipoprotein syndrome is identified. The NLA and other organizations will continue to educate clinicians about the role of apoB measurement in improving clinical risk assessment and dyslipidemia management. An urgent need exists to improve access and reimbursement for apoB testing.

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Background: Insulin resistance (IR) can predict the prognosis of patients suffering from cerebrovascular disorders. The triglyceride-glucose (TyG) index and triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio have been confirmed to be easy and reliable indicators of IR. However, the relationships between the TyG index or TG/HDL-C ratio and early neurological deterioration (END) after thrombolysis in patients with acute ischemic stroke (AIS) are uncertain. Methods: A retrospective analysis of 1,187 patients diagnosed with AIS who underwent intravenous thrombolysis between January 2018 and February 2024 was performed. Post-thrombolysis END was defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) score of ≥4 within 24 h after thrombolysis. Logistic regression analysis was performed to explore the relationships of the TyG index and TG/HDL-C ratio with post-thrombolysis END. Receiver operating characteristic (ROC) analysis was used to assess the ability of the TyG index and TG/HDL-C ratio to discriminate post-thrombolysis END. Results: Among the 1,187 recruited patients, 179 (15.08%) were diagnosed with post-thrombolysis END, and 1,008 (84.92%) were diagnosed with non-END. A binary logistic regression model indicated that the TyG index (odds ratio [OR], 2.015; 95% confidence interval [CI] 1.964-2.414, p = 0.015) and TG/HDL-C ratio (OR, 1.542; 95% CI, 1.160-2.049, p = 0.004) were independent factors for post-thrombolysis END. The area under the curve (AUC) values for the TyG index, TG/HDL-C ratio, and TyG index combined with the TG/HDL-C ratio for post-thrombolysis END were 0.704, 0.674, and 0.755, respectively. Conclusion: This study indicates that the TyG index and TG/HDL-C ratio can be used as prognostic factors to predict post-thrombolysis END.

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BACKGROUND: High-density lipoprotein cholesterol (HDL-C) is widely recognized for its protective effects against cognitive decline. However, recent studies have presented conflicting results, with some suggesting no significant cognitive benefits or even an increased risk of dementia associated with high HDL-C levels. For those who suffer from depression, the cognitive benefits of HDL-C may be diminished or reversed. The purpose of this study is to investigate the associations between HDL-C, cognitive ability, and depressive symptoms in middle-aged and older Chinese adults. METHODS: The datasets utilized were sourced from the China Health and Retirement Longitudinal Study (CHARLS) for the years 2011 and 2015, comprising 4,302 participants. Cross-lagged models were employed to explore the temporal sequence between cognitive performance and HDL-C levels, and to examine the interplay among depression, cognition, and HDL-C. Confounding factors such as sociodemographic characteristics, sleep conditions, and history of chronic diseases were controlled for. RESULTS: The analysis revealed unidirectional effects of baseline impaired cognition and greater severity of depression on increased HDL-C levels at follow-up (ß = - 0.036 and ß = 0.028, respectively, P < 0.05). However, higher baseline HDL-C levels did not significantly predict cognitive performance or depression 4 years later (ß = - 0.008 and ß = 0.023, respectively, P > 0.05). Depressive symptoms and cognition were found to have a significant bidirectional association (ß = - 0.026 and ß = - 0.053, respectively, P < 0.05). CONCLUSIONS: Cognitive impairment and depression are associated with higher HDL-C levels, whereas higher HDL-C levels do not appear to protect against cognitive decline or depressive symptoms. These findings underscore the importance of preserving cognitive and mental health, which may lower the likelihood of cardiovascular disease and dementia. Future studies should validate these findings and develop targeted interventions tailored to specific populations.

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Many studies have reported a relationship between various lipids, such as cholesterol, fatty acids, and lipoproteins, and cardiovascular events. Low-density lipoprotein cholesterol (LDL-C) is often cited as a representative marker. However, there is still room for discussion regarding which markers, among other lipids, should take clinical precedence.This observational study focused on patients without residual stenosis on post-coronary angiography. It was based on blood tests, including lipid profiles at that time, and assessed the association with the subsequent occurrence of major adverse cardiovascular events (MACE, a composite of all-cause mortality, hospitalization due to heart failure, myocardial infarction, stroke, and all revascularizations).Of the 375 patients analyzed, 134 experienced MACE (median follow-up duration: 1031 days). When comparing the MACE and non-MACE groups, significant differences were observed in lipid markers such as non-high-density lipoprotein cholesterol (non-HDL-C) and remnant-like particle cholesterol (RLP-C) (non-HDL-C; P = 0.003, RLP-C; P < 0.001). Furthermore, the area under the curve for RLP-C was 0.656 (95% CI: 0.598-0.714). Improvement in MACE risk discrimination was observed when LDL-C was replaced with non-HDL-C or RLP-C, in addition to atherosclerosis risk factors (non-HDL-C; net reclassification improvement (NRI) = 0.366, 95% CI: 0.159-0.572, RLP-C; NRI = 0.224, 95% CI: 0.016-0.433).It is highly likely that non-HDL-C and RLP-C can serve as significant lipid markers for predicting the occurrence of MACE.

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BACKGROUND: Factors related to depression differ depending on the population studied, and studies focusing on the population of non-manual workers are lacking. Thus, we aimed to identify the risk factors related to depression in non-manual workers in China. METHOD: A large-scale cross-sectional survey was conducted between January 1, 2015 and December 31, 2020, which included 264,557 non-manual workers from one large physical examination institution in China. The Patient Health Questionnaire (PHQ-2) was used to measure depression. A total of 73 variables covering aspects of sociodemographic characteristics, general examination data, health history, symptoms, eating habits, work situation, general sleep conditions and laboratory findings were included in the collection and analysis. Machine learning algorithms of neural networks and logistic regressions were used to assess the risk of depression and explore its factors. RESULTS: Age, feeling fatigue, sleep quality, overeating, waist-to-hip ratio (WHR), and high-density lipoprotein cholesterol (HDLC) were found to be factors of depression. Two prediction models for depression among Chinese non-manual workers were developed with good AUC (0.820), accuracy (0.943), sensitivity (0.743-0.773), and specificity (0.700-0.729). LIMITATIONS: Data were collected at one time point only, meaning that this study cannot explain the causality of the factor on depression. CONCLUSIONS: Our finding that age, feeling fatigue, sleep quality, overeating, WHR, and HDL-C were risk factors for depression in non-manual workers may provide strong evidence for health care facilities to develop preventive measures or government policies for non-manual workers.

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High-sensitivity C-reactive protein (hsCRP) to high-density lipoprotein cholesterol (HDL-C) ratio (CHR) is associated with coronary artery disease (CAD), but its predictive value for long-term adverse outcomes in patients with CAD following percutaneous coronary intervention (PCI) remains unexplored and is the subject of this study. Patients with CAD who underwent PCI at the Korea University Guro Hospital-Percutaneous Coronary Intervention (KUGH-PCI) Registry since 2004 were included. Patients were categorized into tertiles according to their CHR. The end points were all-cause mortality (ACM), cardiac mortality (CM) and major adverse cardiac events (MACEs). Kaplan-Meier analysis, multivariate Cox regression, restricted cubic spline (RCS) and sensitivity analyses were performed. A total of 3260 patients were included and divided into Group 1 (CHR <0.830, N = 1089), Group 2 (CHR = 0.830-3.782, N = 1085) and Group 3 (CHR >3.782, N = 1086). Higher CHR tertiles were associated with progressively greater risks of ACM, CM and MACEs (log-rank, p < 0.001). Multivariate Cox regression showed that patients in the highest tertile had greater risks of ACM (HR: 2.127 [1.452-3.117]), CM (HR: 3.575 [1.938-6.593]) and MACEs (HR: 1.337 [1.089-1.641]) than those in the lowest tertile. RCS analyses did not reveal a significant non-linear relationship between CHR and ACM, CM or MACEs. The significant associations remained significant in the sensitivity analyses, RCS analyses with or without extreme values, subgroup analyses and multiple imputations for missing data. Elevated CHR is a novel, independent risk factor for long-term ACM, CM and MACEs in CAD patients following PCI.

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BACKGROUND: Predictors of neoatherosclerosis in patients who received primary percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) remain unclear. OBJECTIVE: The aim of this study is to investigate the frequency and risk factors of neoatherosclerosis 1-year after the onset of ACS. METHODS: This study investigated 83 patients who underwent PCI for ACS followed by 1-year follow-up optical coherence tomography. The patients were categorized into the neoatherosclerosis (n = 11) and non-neoatherosclerosis groups (n = 72). Baseline characteristics, PCI procedures, medical therapies, and blood tests at 1-year, including detailed lipid profiles, were compared between the two groups. RESULTS: Diabetes mellitus was more prominent in the neoatherosclerosis than in the non-neoatherosclerosis group (45% vs. 17 %, respectively, p = 0.03). Total cholesterol (171 ± 37 mg/dL vs. 145 ± 25 mg/dL, respectively, p < 0.01), non-high-density lipoprotein cholesterol (HDL-C) (124 ± 36 mg/dL vs. 94 ± 24 mg/dL, respectively, p < 0.01), low-density lipoprotein cholesterol (94 ± 36 mg/dL vs. 72 ± 19 mg/dL, respectively, p < 0.01), and lipoprotein (a) (Lp[a]) (70 [19-112] mg/dL vs. 10 [3-25] mg/dL, respectively, p = 0.03) at follow-up were significantly higher in the neoatherosclerosis group. Multivariate analysis revealed that neoatherosclerosis was associated with high serum non-HDL-C (odds ratio [OR]: 1.075; 95 % confidence interval [CI]: 1.011-1.144; p < 0.01) and high serum Lp(a) levels (>30 mg/dL) (OR: 11.0; 95 % CI: 1.492-81.02; p = 0.02). CONCLUSION: Poorly controlled non-HDL-C and Lp(a) would be risk factors of neoatherosclerosis in patients 1-year after ACS.

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Background: The role of high-density lipoprotein cholesterol (HDL-C) in heart failure (HF) outcomes is contentious. We aimed to assess HDL-C's prognostic value in HF patients. Methods: In this retrospective cohort study (2012-2022) at the First Affiliated Hospital of Xinjiang Medical University, we analyzed 4442 patients, categorized by HDL-C quartiles. We applied the Cox proportional hazards model to assess survival and report hazard ratios (HR) with 95% confidence intervals (CI). Results: Over a decade, we recorded 1354 fatalities (42.3%) and 820 readmissions. The third HDL-C quartile (0.93-1.14 mmol/L) showed the lowest mortality rates, with reduced risks in the second and third quartiles compared to the first (Q2 HR=0.809, 95% CI 0.590-1.109; Q3 HR=0.794, 95% CI 0.564-1.118). The fourth quartile presented a lower mortality risk compared to the first (Q4 HR=0.887, 95% CI 0.693-1.134). A significant correlation existed between HDL-C levels and cardiovascular risk (HR=0.85, 95% CI 0.75-0.96, p<0.01). Conclusion: HDL-C levels exhibit a complex association with mortality in HF, indicating the importance of HDL-C in HF prognosis and the need for tailored management strategies.

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BACKGROUND: A persistent redox state and excessive reactive species involved in carbohydrate and lipid metabolism lead to oxidative damage in the liver, however, how fasting plasma concentrations of lipids and glucose are associated with fasting blood levels of alanine transaminase (ALT) and aspartate transaminase (AST) remains to be evaluated in large-scale population. METHODS: A cross-sectional study with 182,971 residents aged 18 to 92 years; multidimensional stratified analyses including quantile linear regression analysis and sex stratification were adopted to improve the quality of the evidence. RESULTS: The associations between the concentrations of non-HDL-C and triglyceride and ALT levels were positive, stronger in males in each quantile of ALT levels and the coefficients expanded with increasing ALT levels at slopes of 3.610 and 5.678 in males and 2.977 and 5.165 in females, respectively. The associations between the HDL-C concentrations and ALT levels were negative, also stronger in males in each quantile and the coefficients expanded with increasing ALT levels at slopes of -7.839 in females and - 5.797 in males. The associations between glucose concentrations and ALT levels were positive, but stronger in females in each quantile and the coefficients expanded with increasing ALT levels at slopes of 1.736 in males and 2.177 in females, respectively. Similar pattern consist of relatively weaker coefficients and slops were observed between concentrations of non-HDL-C, triglyceride and glucose and AST levels. The associations between albumin concentration and concentrations of blood lipids and glucose were relatively steady across all quantiles. CONCLUSIONS: The dose dependent effect between blood concentrations of lipids and glucose and liver function changes suggests that excessive carbohydrate and lipid metabolism may cause subclinical liver damage. Long term sustained primary and secondary inflammatory factors produced in the liver might be transmitted to adjacent organs, such as the heart, kidneys, and lungs, to cause and/or exacerbate pathological changes in these visceral organs.

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BACKGROUND: Numerous studies have demonstrated shared risk factors and pathophysiologic mechanisms between osteoporosis and cardiovascular disease. High-density lipoprotein cholesterol (HDL-C) and platelets have long been recognized as crucial factors for cardiovascular health. The platelet to HDL-C ratio (PHR) combines platelet count and high-density lipoprotein cholesterol (HDL-C) level, It is a novel biomarker for metabolic syndrome and cardiovascular disease. The platelet to HDL-C ratio (PHR) possibly reflects the balance between proinflammatory and anti-inflammatory states in the body. Therefore, we hypothesized that changes in PHR ratios may predict a predisposition to pro-inflammatory and increased bone resorption. However, the relationship between the platelet to HDL-C ratio (PHR) and bone mineral density (BMD) remains insufficiently understood. This study aimed to elucidate the relationship between the platelet to HDL-C ratio (PHR) index and bone mineral density (BMD). METHODS: Data from the NHANES 2005-2018 were analyzed, excluding adults with missing key variables and specific conditions. Nonlinear relationships were explored by fitting smoothed curves and generalized additive models, with threshold effects employed to calculate inflection points. Additionally, subgroup analyses and interaction tests were conducted. RESULTS: The study included 13,936 individuals with a mean age of 51.19 ± 16.65 years. Fitted smoothed curves and generalized additive models revealed a nonlinear, inverted U-shaped relationship between the two variables. Threshold effect analysis showed a significant negative association between PHR and total femur bone mineral density (BMD) beyond the inflection point of platelet to HDL-C ratio (PHR) 33.301. Subgroup analyses showed that a significant interaction between these two variables was observed only in the age and sex subgroups (P-interaction < 0.05). CONCLUSIONS: Our study identified a complex, nonlinear, inverted U-shaped relationship between platelet to HDL-C ratio (PHR) and total femur bone mineral density (BMD). These findings underscore the importance of maintaining optimal PHR levels to support bone health, especially in high-risk populations.

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BACKGROUND: The neutrophil-to-high-density lipoprotein cholesterol ratio (NHR) has emerged as a promising biomarker for assessing inflammation and lipid dysregulation. Increasing evidence indicates that these metabolic disturbances play a crucial role in the development of metabolic dysfunction-associated steatotic liver disease(MASLD). This study aims to investigate the association between NHR, MASLD, and liver fibrosis. METHODS: This cross-sectional study analyzed data from the 2017-2020 National Health and Nutrition Examination Survey (NHANES). Weighted multivariate logistic regression models were used to investigate the association between NHR and both MASLD and liver fibrosis. Smoothed curve fitting and threshold effect analysis were performed to detect potential nonlinear relationships. Subgroup analyses were conducted to assess the consistency of these associations across different groups. RESULTS: The study involved 4,761 participants. We observed a significant positive association between NHR and MASLD (OR = 1.20, 95% CI: 1.09-1.31). However, there was no significant association between NHR and liver fibrosis (OR = 1.01; 95% CI: 0.94-1.09). The analysis of smoothed curve fitting and threshold effect revealed an inverted U-shaped relationship between NHR and MASLD, with a turning point at 5.63. CONCLUSION: Our findings indicate a positive correlation between elevated NHR levels and MASLD prevalence. However, we did not observe a significant association between NHR and liver fibrosis prevalence. Further prospective research is needed to validate these findings in a longitudinal setting.

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BACKGROUND: Limited observational research has explored the relationship between the non-high-density lipoprotein cholesterol (non-HDL-C) to high-density lipoprotein cholesterol (HDL-C) ratio (NHHR) and the risk of post-stroke depression (PSD). This study aims to investigate the potential associations between NHHR and PSD. METHODS: A cross-sectional study was conducted using data from stroke participants aged 20 and older, sourced from the National Health and Nutrition Examination Survey (NHANES) spanning 2005 to 2018. Depression was assessed using the PHQ-9 questionnaire. The association between NHHR and PSD risk was evaluated through weighted multivariate logistic regression and restricted cubic spline (RCS) models. Subgroup and sensitivity analyses were performed to validate the findings. RESULTS: In the continuous model, the NHHR value for the PSD group (3.23±1.84) was significantly higher than that of the non-PSD group (2.79±1.40, p=0.015). Logistic regression analysis in the fully adjusted model revealed a positive association between NHHR and PSD (OR 1.16, 95 % CI 1.03-1.30, p=0.016). Interaction tests showed no significant differences across strata (p > 0.05 for interaction). Restricted cubic spline results indicated a linear dose-response relationship between NHHR and PSD risk (P for non-linearity = 0.6). This association persisted in various subgroup analyses. CONCLUSION: NHHR was significantly correlated with an increased risk of PSD among U.S. adults. Further re-search on NHHR could contribute to the prevention and treatment of PSD.

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BACKGROUND: Although high-density lipoprotein cholesterol (HDL-C) exerts a significant influence on the development of metabolic dysfunction-associated fatty liver disease (MAFLD), the association of dynamic changes in HDL-C levels with the risk of MAFLD remains unclear. Thus, the aim of the current study was to explore the association between the changing trajectories of HDL-C and new-onset MAFLD. The findings of this study may provide a theoretical basis for future personalized intervention and prevention targeting MAFLD. METHODS: A total of 1507 participants who met the inclusion criteria were recruited from a community-based physical examination population in Nanjing, China from 2017 to 2021. Group-based trajectory models were constructed to determine the heterogeneous HDL-C trajectories. The incidence of MAFLD in each group in 2022 was followed up, and the Cox proportional hazards regression model was applied to investigate the associations between different HDL-C trajectories and the risk of new-onset MAFLD. RESULTS: The incidences of MAFLD in the low-stable, moderate-stable, moderate-high-stable, and high-stable groups of HDL-C trajectory were 26.5%, 13.8%, 7.2% and 2.6%, respectively. The incidence rate of MAFLD in the order of the above trajectory groups exhibited a decreasing trend (χ2 = 72.55, Ptrend<0.001). After adjusting for confounders, the risk of MAFLD onset in HDL-C low-stable group was still 5.421 times (95%CI: 1.303-22.554, P = 0.020) higher than that in the high-stable group. Subgroup analyses of the combined (moderate high-stable and high-stable groups combined), moderate-stable and low-stable groups showed that sex, age, and overweight/obesity did not affect the association between HDL-C trajectory and MAFLD risk. CONCLUSIONS: Persistently low HDL-C level is a risk factor for the onset of MAFLD. Long-term monitoring of HDL-C levels and timely intervention for those experiencing persistent declines are crucial for early prevention of MAFLD.

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BACKGROUND: Serum lipids are highly heritable and play an important role in cardiovascular and metabolic health. However, the relationship between high-density lipoprotein cholesterol (HDL-C) and serum 25-hydroxyvitamin D [25(OH)D] levels is unclear. This study aims to explore the association between serum 25(OH)D levels and HDL-C in adults aged 20-59. METHODS: This cross-sectional study was based on data from the National Health and Nutrition Examination Survey (NHANES). Multivariable logistic regression was used to assess the relationship between HDL-C and serum 25(OH)D, with further analysis using smooth spline fitting and generalized additive models. RESULTS: A total of 28,084 adults were included in the study. After adjusting for multiple variables, we found a significant positive correlation between HDL-C and serum 25(OH)D levels (ß = 8.3, 95% CI: 7.24-9.35, p < 0.001). Stratified subgroup analysis by gender showed that females consistently exhibited a positive correlation (ß = 10.12, 95% CI: 9.07-11.18, p < 0.001), while males demonstrated an inverted U-shaped relationship between HDL-C and serum 25(OH)D. CONCLUSION: In the population aged 20-59, HDL-C levels are significantly associated with serum 25(OH)D levels. Clinically, simultaneous monitoring of HDL-C and vitamin D is recommended to better assess and manage cardiovascular health. Increasing vitamin D intake should be considered, especially for males with low HDL-C levels, to prevent related health issues.

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BACKGROUND: Recent studies have demonstrated that very high high-density lipoprotein cholesterol (HDL-C) level was paradoxically linked with higher risk of cardiovascular mortality, all-cause mortality, and several age-related diseases. However, whether very high HDL-C level is associated with a higher risk of sarcopenia in older adults remains unclear. We aimed to investigate the association between HDL-C level and the risk of developing sarcopenia and low grip strength over time in older adults. METHODS: Participants were from the ongoing China Health and Retirement Longitudinal Study (CHARLS), which includes a nationally representative sample of adults aged ≥45 years and was performed from 2011 to 2020 with follow-ups every two to three years. The current study included 4031 participants aged ≥60 years. Muscle health-related data were collected in waves 2011, 2013, and 2015. Based on HDL-C level at baseline, participants were categorized into five groups: <35 mg/dl, 35-40 mg/dl, 40-60 mg/dl, 60-70 mg/dl and >70 mg/dl. The main outcomes were incident sarcopenia and incident low grip strength over follow-up. Low grip strength and sarcopenia were defined according to the 2019 Consensus by the Asian Working Group for Sarcopenia. Cox proportional-hazard regression was performed to investigate the association between HDL-C level and the risk of developing sarcopenia and low grip strength in older adults. RESULTS: The mean age of study sample was 67.3 (SD 6.1) years, and 49.6% were male. During an average 3.7-year follow-up, 409 (10.1%) participants developed sarcopenia and 771 (21.1%) developed low grip strength. Non-linear association was observed between HDL-C level and the hazard of developing sarcopenia and low grip strength. The multivariable model showed that compared to the reference group (40-60 mg/dl), older adults with very high HDL-C level (>70 mg/dl) had a significantly higher risk of developing sarcopenia (HR 1.69, 95% CI 1.28-2.23) and low grip strength (HR 1.23 95% CI 1.00-1.51). Stratified analyses by sex revealed similar association. CONCLUSIONS: We present the first longitudinal evidence that very high HDL-C level was associated with a significantly higher risk of muscle strength decline and developing sarcopenia in older adults. It is essential to monitor the muscle health of older adults with very high HDL-C level in clinical practice.

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BACKGROUND AND OBJECTIVE: The value of the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) assessment in the context of metabolic abnormalities is growing in importance. Nevertheless, the relationship between NHHR and hyperuricemia (HUA) is unknown. This study seeks to investigate the relationship between NHHR and HUA. METHODS: The data derived from the 2017-2020 National Health and Nutrition Examination Survey (NHANES) included 7,876 adult participants. The multivariable logistic regression model, subgroup analysis and smooth fitting curve were utilized in order to investigate the association between NHHR and HUA. RESULTS: In the fully adjusted model 3, NHHR was significantly associated with HUA. Specifically, participants in the highest quartile of NHHR had 1.95 times higher odds of HUA prevalence compared to those in the lowest quartile [2.95 (2.39, 3.64), P < 0.0001]. Although the overall trend suggested a positive association, further analysis using smooth fitting curves and threshold effect analysis indicated that this association was nonlinear, with an inflection point at 5.8. The positive association persisted across different HUA definitions and after removing outliers. Subgroup analysis showed significant interactions between NHHR and HUA in different races and diabetes statuses. The odds of HUA prevalence were higher among non-diabetic participants [1.40 (1.32, 1.49), P < 0.0001] compared to diabetic participants [1.18 (1.06, 1.32), P = 0.0031]. Mexican Americans had the lowest odds of HUA prevalence [1.09 (0.92, 1.27), P = 0.2413] compared to other races. CONCLUSIONS: There is a significant positive association between NHHR and HUA, indicating that NHHR may serve as a potential risk assessment maker for HUA, although further prospective studies are needed for validation.

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OBJECTIVES: Some anti-seizure medications (ASMs) are known to induce liver enzymes and impact lipid values that include total cholesterol (TC), low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), and triglyceride (TG). In addition, use of ketogenic diet therapies, including the modified Atkins diet (MAD), has also influenced lipids. Here, we explored the combined impact of enzyme inducing ASMs (EIASMs) and MAD on lipid values in adults with epilepsy. METHODS: Diet-naïve adults with epilepsy who began MAD were divided into three groups based on ASM use: EIASMs, non-EIASMs, and those on no ASMs. Demographic information, epilepsy-specific clinical history, anthropometrics and lipid values were obtained through retrospective chart review at baseline and after a minimum of 12 months of MAD use. RESULTS: Forty-two adults on MAD had baseline and follow up 12-month lipid outcomes. There was a significant increase in median levels of TC, LDL, non-HDL, and HDL after 12 months of MAD use. There was no change in median levels of TG. When separated according to ASM category, adults on non-EIASMs showed significant elevations in TC, HDL, and LDL after 12 months of MAD use. In contrast, adults on EIASMs only showed a significant increase in HDL after 12 months of MAD use. DISCUSSION: The increase in atherogenic cholesterol levels observed after 12 months of MAD use was most pronounced in adults with epilepsy on non-EIASMs and not observed in adults with epilepsy on EIASMs despite a higher proportion of abnormal cholesterol levels at baseline in those on EIASMs.

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BACKGROUND: Glycotoxicity and lipotoxicity are key pathophysiological mechanisms underlying the development of metabolic associated fatty liver disease (MAFLD). The primary objective of this study is to investigate the association between the newly proposed Plasma-Glycosylated Hemoglobin A1c/High-Density Lipoprotein Cholesterol Ratio (HbA1c/HDL-C ratio) and the risk of MAFLD. METHODS: A study population of 14,251 individuals undergoing health examinations was included. The association between the HbA1c/HDL-C ratio and MAFLD was analyzed using multivariable logistic regression and restricted cubic spline (RCS) analysis. Exploratory analyses were conducted to assess variations in this association across subgroups stratified by gender, age, body mass index (BMI), exercise habits, drinking status, and smoking status. The discriminatory value of the HbA1c/HDL-C ratio and its components for screening MAFLD was evaluated using receiver operating characteristic (ROC) curves. RESULTS: A total of 1,982 (13.91%) subjects were diagnosed with MAFLD. After adjusting for confounding factors, we found a significant positive association between the HbA1c/HDL-C ratio and MAFLD [odds ratio (OR) 1.34, 95% confidence interval (CI): 1.25, 1.44]. No significant differences in this association were observed across all subgroups (All P for interaction > 0.05). Furthermore, through RCS analysis, we observed a nonlinear positive correlation between the HbA1c/HDL-C ratio and MAFLD (P for non-linearity < 0.001), with a potential threshold effect point (approximately 3 for the HbA1c/HDL-C ratio). Beyond this threshold point, the slope of the MAFLD prevalence curve increased rapidly. Additionally, in further ROC analysis, we found that for the identification of MAFLD, the HbA1c/HDL-C ratio was significantly superior to HbA1c and HDL-C, with an area under the curve (AUC) and optimal threshold of 0.81 and 4.08, respectively. CONCLUSIONS: Our findings suggest that the newly proposed HbA1c/HDL-C ratio serves as a simple and practical indicator for assessing MAFLD, exhibiting well-discriminatory performance in screening for MAFLD.

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Metabolic syndrome has been associated with reduced brain white matter integrity in older individuals. However, less is known about how metabolic syndrome might impact white matter integrity in younger populations. This study examined metabolic syndrome-related global and regional white matter integrity differences in a sample of 537 post-9/11 Veterans. Metabolic syndrome was defined as ≥3 factors of: increased waist circumference, hypertriglyceridemia, low high-density lipoprotein cholesterol, hypertension, and high fasting glucose. T1 and diffusion weighted 3 T MRI scans were processed using the FreeSurfer image analysis suite and FSL Diffusion Toolbox. Atlas-based regions of interest were determined from a combination of the Johns Hopkins University atlas and a Tract-Based Spatial Statistics-based FreeSurfer WMPARC white matter skeleton atlas. Analyses revealed individuals with metabolic syndrome (n = 132) had significantly lower global fractional anisotropy than those without metabolic syndrome (n = 405), and lower high-density lipoprotein cholesterol levels was the only metabolic syndrome factor significantly related to lower global fractional anisotropy levels. Lobe-specific analyses revealed individuals with metabolic syndrome had decreased fractional anisotropy in frontal white matter regions compared with those without metabolic syndrome. These findings indicate metabolic syndrome is prevalent in this sample of younger Veterans and is related to reduced frontal white matter integrity. Early intervention for metabolic syndrome may help alleviate adverse metabolic syndrome-related brain and cognitive effects with age.

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Atherosclerosis (AS) is one of the most common causes of death from cardiovascular disease, and low folic acid (FA) levels have been reported to be strongly associated with an increased risk of AS. We aimed to obtain causal estimates of the association between FA and AS and to quantify the mediating role of known modifiable risk factors. Based on the largest genome-wide association study (GWAS) from the IEU Open GWAS Project for all human studies, we conducted a two-sample Mendelian randomization (MR) study of genetically predicted FA and AS. A two-step MR design was then used to assess the causal mediating effect of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) on the relationship between FA and AS. This MR analysis showed that genetically determined FA levels [IVW: Odds Ratio (OR) = 0.623, 95% CI 0.421-0.924, P = 0.018] were associated with a reduced risk of AS. Inverse variance weighted (IVW) MR analysis also showed that genetically predicted FA was positively correlated with HDL-C levels (OR = 1.358, 95% CI 1.029-1.792, P = 0.031) and negatively correlated with LDL-C (OR = 0.956, 95% CI 0.920-0.994, P = 0.023) and TG levels (OR = 0.929, 95% CI 0.886-0.974, P = 0.003). LDL-C, HDL-C, and TG mediate 3.00%, 6.80%, and 4.40%, respectively, of the total impact of FA on AS. The combined effect of these three factors accounts for 13.04% of the total effect. Sensitivity analysis verifies the stability and reliability of the results. These results support a potential causal protective effect of FA on AS, with considerable mediation through many modifiable risk factors. Thus, interventions on levels of LDL-C, HDL-C, and TG have the potential to substantially reduce the burden of AS caused by low FA.

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